Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone

During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly

Flat feline faces: is brachycephaly associated with respiratory abnormalities in the domestic cat (Felis catus)?

There has been little research into brachycephalism and associated disorders in cats. A questionnaire aimed at cat owners was used to determine the relationship between feline facial conformation and owner-reported cat management requirements and respiratory abnormalities. Owner-submitted photographs of cats were used to develop novel measures of skull conformation. One thousand valid questionnaires were received. Within these there were 373 valid photographs that allowed measurement of muzzle ratio (M%) and 494 that allowed nose position ratio (NP%). The data included 239 cats for which both measurements were available. Owners reported lifestyle factors (e.g. feeding type, grooming routine, activity level), physical characteristics (e.g. hair length) and other health characteristics of their cat (e.g. tear staining, body condition score). A composite respiratory score (RS) was calculated for each cat using their owner’s assessment of respiratory noise whilst their cat was asleep and then breathing difficulty following activity. Multivariate analyses were carried out using linear models to explore the relationship between RS and facial conformation, and lifestyle risk factors. The results showed that reductions in NP% and M% were significantly associated with RS (P < 0.001 and P = 0.026, respectively) and that the relationship was significantly negatively correlated (r = -0.56, P < 0.001 for both). Respiratory score was also significantly associated with increased presence of tear staining (P < 0.001) and a sedentary lifestyle (P = 0.01). This study improves current knowledge concerning cats with breeding-related alterations in skull confirmation and indicates that brachycephalism may have negative respiratory implications for cat health and welfare, as has been previously shown in dogs

A tiered-layered-staged model for informed consent in personal genome testing

In recent years, developments in genomics technologies have led to the rise of commercial personal genome testing (PGT): broad genome-wide testing for multiple diseases simultaneously. While some commercial providers require physicians to order a personal genome test, others can be accessed directly. All providers advertise directly to consumers and offer genetic risk information about dozens of diseases in one single purchase. The quantity and the complexity of risk information pose challenges to adequate pre-test and post-test information provision and informed consent. There are currently no guidelines for what should constitute informed consent in PGT or how adequate informed consent can be achieved. In this paper, we propose a tiered-layered-staged model for informed consent. First, the proposed model is tiered as it offers choices between categories of diseases that are associated with distinct ethical, personal or societal issues. Second, the model distinguishes layers of information with a first layer offering minimal, indispensable information that is material to all consumers, and additional layers offering more detailed information made available upon request. Finally, the model stages informed consent as a process by feeding information to consumers in each subsequent stage of the process of undergoing a test, and by accommodating renewed consent for test result updates, resulting from the ongoing development of the science underlying PGT. A tiered-layered-staged model for informed consent with a focus on the consumer perspective can help overcome the ethical problems of information provision and informed consent in direct-to-consumer PGT.European Journal of Human Genetics advance online publication, 21 November 2012; doi:10.1038/ejhg.2012.237

Persian cats under first opinion veterinary care in the UK:demography, mortality and disorders

Persian cats are a popular cat breed worldwide, and especially in the US, Europe and Asia. This study aimed to describe the demography, common disorders and mortality in Persians under general practice veterinary care in 2013 in the UK. The study population of 285,547 cats overall included 3235 (1.1%) Persians. Mean adult Persian bodyweight was 3.9 kg (SD 0.9) and median age was 7.0 years (IQR 3.3–11.6). At least one disorder was recorded in 2099 (64.9%) Persians. The most common specific disorders were haircoat disorders (411, 12.7%), periodontal disease (365, 11.3%), overgrown nails (234, 7.2%), and ocular discharge (188, 5.8%). The most common disorder groups were dermatological (578, 17.9%), ophthalmological (496, 15.3%) and dental (397, 12.3%). Median longevity was 13.5 years (IQR 9.9–16.0). The most common grouped causes of death were renal disease (102, 23.4%), neoplasia (37, 8.5%) and mass-associated disorder (35, 8.0%). This is the first study to use general practice data to examine the overall health of Persian cats. With haircoat, ocular and dental disorders being the predominant disorders identified, this study highlights the need for increased owner awareness to manage and prevent the typical health problems associated with this breed’s phenotype

Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task

RATIONALE: Nicotinic receptors have been implicated in attentional performance. Nicotine can improve attention in animals and humans, but knowledge about relevant receptor subtypes is very limited. OBJECTIVES: The aim was to examine the role of α7 receptors in attentional performance of mice and in effects of nicotine. MATERIALS AND METHODS: Mice with targeted deletion of the gene coding for the α7 subunit of nicotinic receptors and wild-type controls were trained on a five-choice serial reaction time task with food reinforcers presented under varying parametric conditions. Nicotine was administered in a range of doses (0.001–1.0 mg/kg sc), including those reported to enhance attentional performance. RESULTS: Initially the α7(−/−) (knockout) mice responded less accurately and made more anticipatory responses. After task parameters were altered so that the time allowed for responding was reduced and anticipatory (impulsive) responses were punished by a time-out, the pattern of performance deficits changed; there were increased omission errors in α7(−/−) mice but normal levels of accuracy and anticipatory responding. Nicotine did not improve any measure of performance, either with the original training parameters or after retraining; the largest dose used (1.0 mg/kg) produced a general impairment of responding in α7(−/−) and wild-type mice. CONCLUSIONS: α7 nicotinic receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a possible role for α7 receptors in attentional processing. However, identification of a protocol for assessing attention-enhancing effects of nicotine in mice may require further modifications of test procedures or the use of different strains of animal

Financial and monetary policy responses to oil price shocks: evidence from oil-importing and oil-exporting countries

In this study, we investigate the financial and monetary policy responses to oil price shocks using a Structural VAR framework. We distinguish between net oil-importing and net oil-exporting countries. Since the 80s, a significant number of empirical studies have been published investigating the effect of oil prices on macroeconomic and financial variables. Most of these studies though, do not make a distinction between oil-importing and oil-exporting economies. Overall, our results indicate that the level of inflation in both net oil-exporting and net oil-importing countries is significantly affected by oil price innovations. Furthermore, we find that the response of interest rates to an oil price shock depends heavily on the monetary policy regime of each country. Finally, stock markets operating in net oil-importing countries exhibit a negative response to increased oil prices. The reverse is true for the stock market of the net oil-exporting countries. We find evidence that the magnitude of stock market responses to oil price shocks is higher for the newly established and/or less liquid stock market

Stab Injury to the Preauricular Region With Laceration of the External Carotid Artery Without Involvement of the Facial Nerve: a Case Report

BACKGROUND: Open injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external carotid artery. Hence, external carotid artery lesions are usually associated with facial nerve dysfunction. We present an unusual case report in which the patient had an injury to this artery with no facial nerve compromise. CASE PRESENTATION: A 25-year-old Portuguese man sustained a stab wound injury to his right preauricular region with a broken glass. Immediate profuse bleeding ensued. Provisory tamponade of the wound was achieved at the place of aggression by two off-duty doctors. He was initially transferred to a district hospital, where a large arterial bleeding was observed and a temporary compressive dressing was applied. Subsequently, the patient was transferred to a tertiary hospital. At admission in the emergency room, he presented a pulsating lesion in the right preauricular region and slight weakness in the territory of the inferior buccal branch of the facial nerve. The physical examination suggested an arterial lesion superficial to the facial nerve. However, in the operating theater, a section of the posterior and lateral flanks of the external carotid artery inside the parotid gland was identified. No lesion of the facial nerve was observed, and the external carotid artery was repaired. To better understand the anatomical rationale of this uncommon clinical case, we dissected the preauricular region of six cadavers previously injected with colored latex solutions in the vascular system. A small triangular space between the two main branches of division of the facial nerve in which the external carotid artery was not covered by the facial nerve was observed bilaterally in all cases. CONCLUSIONS: This clinical case illustrates that, in a preauricular wound, the external carotid artery can be injured without facial nerve damage. However, no similar description was found in the reviewed literature, which suggests that this must be a very rare occurrence. According to the dissection study performed, this is due to the existence of a triangular space between the cervicofacial and temporofacial nerve trunks in which the external carotid artery is not covered by the facial nerve or its branches.info:eu-repo/semantics/publishedVersio